Abstract
For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r2) and prediction accuracy (rCV2) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.
Keywords: 18β-glycyrrhetinic acid, QSAR, Docking, Drug likeness, Human lung cancer (A-549), in-vitro cytotoxicity.
Medicinal Chemistry
Title:QSAR and Docking Based Semi-synthesis and in vitro Evaluation of 18 β-glycyrrhetinic Acid Derivatives Against Human Lung Cancer Cell Line A-549
Volume: 9 Issue: 8
Author(s): Dharmendra Kumar Yadav, Komal Kalani, Feroz Khan and Santosh Kumar Srivastava
Affiliation:
Keywords: 18β-glycyrrhetinic acid, QSAR, Docking, Drug likeness, Human lung cancer (A-549), in-vitro cytotoxicity.
Abstract: For the prediction of anticancer activity of glycyrrhetinic acid (GA-1) analogs against the human lung cancer cell line (A-549), a QSAR model was developed by forward stepwise multiple linear regression methodology. The regression coefficient (r2) and prediction accuracy (rCV2) of the QSAR model were taken 0.94 and 0.82, respectively in terms of correlation. The QSAR study indicates that the dipole moments, size of smallest ring, amine counts, hydroxyl and nitro functional groups are correlated well with cytotoxic activity. The docking studies showed high binding affinity of the predicted active compounds against the lung cancer target EGFR. These active glycyrrhetinic acid derivatives were then semi-synthesized, characterized and in-vitro tested for anticancer activity. The experimental results were in agreement with the predicted values and the ethyl oxalyl derivative of GA-1 (GA-3) showed equal cytotoxic activity to that of standard anticancer drug paclitaxel.
Export Options
About this article
Cite this article as:
Yadav Kumar Dharmendra, Kalani Komal, Khan Feroz and Srivastava Kumar Santosh, QSAR and Docking Based Semi-synthesis and in vitro Evaluation of 18 β-glycyrrhetinic Acid Derivatives Against Human Lung Cancer Cell Line A-549, Medicinal Chemistry 2013; 9 (8) . https://dx.doi.org/10.2174/1573406411309080009
DOI https://dx.doi.org/10.2174/1573406411309080009 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
MicroRNAs in Platelet Biogenesis and Function: Implications in Vascular Homeostasis and Inflammation
Current Vascular Pharmacology HIV-1 Vif: HIVs Weapon Against the Cellular Defense Factor APOBEC3G
Current HIV Research Immune Checkpoint Inhibitors in AML-A New Frontier
Current Cancer Drug Targets Bioluminescence Imaging in Rodents: When Light Illuminates Cancer Research
Current Molecular Imaging (Discontinued) pH-Sensitive PEGylated Liposomes Functionalized With a Fibronectin-Mimetic Peptide Show Enhanced Intracellular Delivery to Colon Cancer Cells
Current Pharmaceutical Biotechnology ING Proteins as Potential Anticancer Drug Targets
Current Drug Targets Antimetastatic Activities and Mechanisms of Bisdioxopiperazine Compounds
Anti-Cancer Agents in Medicinal Chemistry Chemokines as Therapeutic Targets in Non-Small Cell Lung Cancer: Update
Medicinal Chemistry Reviews - Online (Discontinued) Novel Approaches Towards Designing of Isoform-Selective Inhibitors Against Class II Histone Deacetylases: The Acute Requirement for Targetted Anticancer Therapy
Current Topics in Medicinal Chemistry Multi-Component Reactions of Cyclohexan-1,3-dione: Synthesis of Fused Pyran, Pyridine, Thiophene and Pyrazole Derivatives with c-Met, Anti-Proliferative Activities
Anti-Cancer Agents in Medicinal Chemistry Molecular Mechanisms of Biological Activity of Oleanolic Acid - A Source of Inspiration for A New Drugs Design
Mini-Reviews in Organic Chemistry Pyridine Based Antitumour Compounds Acting at the Colchicine Site
Current Medicinal Chemistry Anti-Tuberculosis Drug Induced Hepatotoxicity and Genetic Polymorphisms in Drug-metabolizing Genes
Current Pharmacogenomics Screening of Potential Anticancer Compounds from Sargassum wightii to Target Breast Cancer Specific HER2 Receptor using in-silico Analysis
The Natural Products Journal Synthesis, Preferentially Hypoxic Apoptosis and Anti-Angiogenic Activity of 3- Amino-1,2,4-Benzotriazine-1,4-Dioxide Bearing Alkyl Linkers with a 3-Amino-1,2,4- Benzotriazine-1-Oxide Moiety
Anti-Cancer Agents in Medicinal Chemistry Cancer Therapy Based on a Mechanism of Action for Controlling the Immune System and the Resulting Patent Portfolio
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Vascular Disrupting Agents (VDAs) in Anticancer Therapy
Current Clinical Pharmacology Synthesis and Biological Evaluation of 3-Substituted-4-(4-methylthio phenyl)-1HPyrrole Derivatives as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry The Need for Physiologically Relevant Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ) Ligands
Endocrine, Metabolic & Immune Disorders - Drug Targets Microbiome in Chronic Obstructive Pulmonary Disease: Role of Natural Products Against Microbial Pathogens
Current Medicinal Chemistry